The primary objective of our proposed research efforts is to investigate the role of the central nervous system (CNS) in regulating immune responsiveness. To accomplish this goal, electrolytic lesions will be placed in various areas of the brain in Fischer-344 rats. At specific intervals host immunocompetence of these animals and appropriate controls will be assessed using a variety of specific and non-specific, in vivo and in vitro immunologic probes. Neural innervation patterns of lymphoid tissue will be determined by fluorometric methods and lymphoid neurotransmittor levels will be quantitated by microradioenzymatic assays. In addition, the role of catecholamine; serotonin "balance" in influencing immunologic responsiveness will be assessed. Experiments are also presented which is designed to elucidate the mechanisms of neuroimmunomodulation via suppressor cell function, lymphocyte subpopulations and changes in immunologic circadian rhythmicity. The data gathered from these studies will establish the concept of a neurally mediated network which functions as an external control for immunologic homeostasis.